Transvenous method of treating sleep apnea

ABSTRACT

A system and method for treating sleep apnea includes inserting an implantable pulse generator subcutaneously within a body of a patient and connecting a lead to the pulse generator. The lead is inserted within the vasculature and advanced transvenously through the vasculature until a stimulation portion of the lead becomes positioned in close proximity to the hypoglossal nerve. A nerve-stimulation signal is applied to the hypoglossal nerve via the stimulation portion of the lead.

CROSS-REFERENCE TO RELATED APPLICATIONS

This Utility patent application is a U.S. National Stage filing under 35U.S.C. § 371 of PCT/US2009/59060, filed Sep. 30, 2009 and U.S.Provisional Application No. 61/101,952, filed Oct. 1, 2008, both ofwhich are incorporated herein by reference.

BACKGROUND

The present disclosure relates generally to an implantable stimulationsystem for stimulating and monitoring soft tissue in a patient, and moreparticularly, the present disclosure relates to a method of using atransvenous delivery of a stimulation lead to treat sleep apnea.

Sleep apnea generally refers to the cessation of breathing during sleep.One type of sleep apnea, referred to as obstructive sleep apnea (OSA),is characterized by repetitive pauses in breathing during sleep due tothe obstruction and/or collapse of the upper airway, and is usuallyaccompanied by a reduction in blood oxygenation saturation.

One treatment for obstructive sleep apnea has included the delivery ofelectrical stimulation to the hypoglossal nerve, located in the neckregion under the chin. Such stimulation therapy activates the upperairway muscles to maintain upper airway patency. In treatment of sleepapnea, increased respiratory effort resulting from the difficulty inbreathing through an obstructed airway is avoided by synchronizedstimulation of an upper airway muscle or muscle group that holds theairway open during the inspiratory phase of breathing. For example, thegenioglossus muscle is stimulated during treatment of sleep apnea by acuff electrode placed around the hypoglossal nerve.

BRIEF DESCRIPTION OF THE DRAWINGS

Aspects and features of the present disclosure will be appreciated asthe same becomes better understood by reference to the followingdetailed description of the embodiments of the present disclosure whenconsidered in connection with the accompanying drawings, wherein:

FIG. 1 is a schematic illustration of an implantable stimulation system,according to an embodiment of the present disclosure;

FIG. 2A is a schematic illustration of a block diagram of an implantablestimulation system, according to an embodiment of the presentdisclosure;

FIG. 2B is a schematic illustration of a block diagram of a sensingmonitor, according to an embodiment of the present disclosure;

FIG. 3A is a schematic illustration of a transvenous placement of astimulation lead and sensor for treating sleep apnea, according to anembodiment of the present disclosure;

FIG. 3B is a schematic illustration of an array of response evaluationtools and a nerve monitoring system, according to an embodiment of thepresent disclosure;

FIG. 4A is a schematic illustration of a method of stimulating a nervevia multiple venous pathways and/or via multiple stimulation sites,according to an embodiment of the present disclosure;

FIG. 4B is a schematic illustration of a stimulation lead systemincluding multiple independent stimulation leads, according to anembodiment of the present disclosure;

FIG. 5A is a side plan view of an over-the-wire delivery system for astimulation lead, according to an embodiment of the present disclosure;

FIG. 5B is a side plan view of an stylet-driven delivery mechanism for astimulation lead, according to an embodiment of the present disclosure;

FIG. 6 is a schematic illustration of a method of selecting astimulation site, according to an embodiment of the present disclosure;

FIG. 7 is a schematic illustration of a transvenous placement of astimulation lead and sensor for treating sleep apnea, according to anembodiment of the present disclosure;

FIG. 8 is a side plan view of a stimulation lead, according to anembodiment of the present disclosure;

FIG. 9 is a side plan view of a stimulation lead including a coiledconfiguration at a distal portion, according to an embodiment of thepresent disclosure;

FIG. 10 is a perspective view of a distal portion of a stimulation leadincluding an array of ring electrodes, according to an embodiment of thepresent disclosure;

FIG. 11 is a side plan view of a distal portion of a stimulation leadincluding a combined stent-electrode configuration, according to anembodiment of the present disclosure;

FIG. 12A is a side plan view of a distal portion of a stimulation leadincluding an array of selectively deployable tines shown in a deployedconfiguration, according to an embodiment of the present disclosure;

FIG. 12B is a side plan view of the lead of FIG. 12A with the tinesshown in a storage position, according to an embodiment of the presentdisclosure;

FIG. 13 is a perspective view of a distal portion of a stimulation leadincluding a programmable array of electrodes mounted circumferentiallyaround the lead, according to an embodiment of the present disclosure;

FIG. 14 is a perspective view of a distal portion of a stimulation leadincluding an array of programmable ring electrodes, according to anembodiment of the present disclosure;

FIG. 15A is a side plan view schematically illustrating a nervestimulation system, according to an embodiment of the presentdisclosure;

FIG. 15B is a schematic illustration of a transvenous placement of amicrostimulator of the system of FIG. 15A, according to an embodiment ofthe present disclosure;

FIG. 15C is a schematic illustration of a garment configured to providerespiratory sensing for the system of FIGS. 15A-15B, according to anembodiment of the present disclosure;

FIG. 16 is a side plan view schematically illustrating an anchoringsystem of a transvenously delivered microstimulator, according to anembodiment of the present disclosure;

FIG. 17A is a side plan view schematically illustrating a stent-basedanchoring system of a transvenously delivered microstimulator, accordingto an embodiment of the present disclosure;

FIG. 17B is a sectional view schematically illustrating amicrostimulator and a stent of the anchoring system of FIG. 17A,according to an embodiment of the present disclosure; and

FIG. 17C is a side plan view schematically illustrating amicrostimulator and a stent of the anchoring system of FIG. 17A,according to an embodiment of the present disclosure.

DESCRIPTION OF EMBODIMENTS

The following detailed description is merely exemplary in nature and isnot intended to limit the present disclosure or the application and usesof the present disclosure. Furthermore, there is no intention to bebound by any expressed or implied theory presented in the precedingtechnical field, background, or the following detailed description.

Embodiments of the present disclosure provide an implantable medicaldevice for treating obstructive sleep apnea wherein stimulation isprovided to the hypoglossal nerve (or another target nerve) through atransvenous lead system. The stimulation may be provided synchronouswith respiration detected by a sensing lead system. In some embodiments,a single transvenous lead includes both a sensing lead and thestimulation lead, such that the sensing lead is integral with orconnected to the stimulation lead. In other embodiments, the sensinglead forms a transvenous lead separate from a transvenous stimulationlead. In still other embodiments, the sensing lead comprises a sensinglead external to the venous system altogether (such as being mountedexternally on a patient or subcutaneously implanted) while thestimulation lead comprises a transvenous lead.

FIG. 1 is a schematic diagram of an implantable stimulation system thatincludes a transvenously placed stimulation electrode, according to anembodiment of the present disclosure. As illustrated in FIG. 1, anexample of an implantable stimulation system 10 according to oneembodiment of the present disclosure includes an implantable pulsegenerator (IPG) 55, capable of being surgically positioned within apectoral region of a patient 20, and a stimulation lead 52 electricallycoupled with the IPG 55 via a connector (not shown) positioned within aconnection port of the IPG 55. The lead 52 includes a stimulationelectrode portion 65 and extends from the IPG 55 so that the stimulationelectrode portion 65 is positioned within a portion of the vasculatureadjacent a desired nerve, such as the hypoglossal nerve 53 of thepatient 10, to enable stimulation of the nerve 53, as described below indetail. An exemplary implantable stimulation system in which lead 52 maybe utilized, for example, is described in U.S. Pat. No. 6,572,543 toChristopherson et al., and which is incorporated herein by reference inits entirety. In one embodiment, the lead 52 further includes an sensorportion 60 (electrically coupled to the IPG 55 and extending from theIPG 55) positioned in the patient 10 for sensing respiratory effort.

In some embodiments, in addition to the IPG 55 being configured to treatobstructive sleep apnea, the IPG 55 is additionally configured as acardiac therapy device, such as a bradycardia pacemaker, implantablecardiac defibrillator, or cardiac resynchronization therapy device. Inone aspect, one or more leads extend from the IPG 55 to access the heartvia a transvenous approach in order to apply a cardiac therapy. In oneembodiment, one or more of these cardiac therapy configurations of theIPG 55 also have sensors (pressure, impedance) on the cardiac leadswhich may also provide a respiratory signal for use in delivering anobstructive sleep apnea therapy. Exemplary embodiments of an implantablestimulation system for applying a cardiac therapy via transvenousdelivery of a lead is described in Hill et al. U.S. Pat. No. 6,006,134and Cho et al. U.S. Pat. No. 6,641,542, which are both incorporated byreference herein in their entirety.

In one embodiment in which the IPG 55 is configured to treat bothcardiac therapy and sleep apnea, a first lead (or set of leads) extendsfrom the IPG 55 for sensing cardiac activity and detecting cardiacevents while a second lead (or set of leads) extends from the IPG 55 tosense respiratory activity and to detect respiratory events. However, inanother embodiment, only one set of leads is used to sense bothrespiratory activity and cardiac activity. Accordingly, in this latterembodiment, in one configuration, a respiratory signal obtained via acardiac sensing lead is also used to trigger application of astimulation signal when applying an obstructive sleep apnea therapy, andalso optionally is used to monitor and detect apneas.

In some embodiments, instead of using a single IPG to apply both cardiactherapies and sleep apnea therapies, a second implantable pulsegenerator (IPG 55) is implanted (in addition to the first IPG) so thatone IPG 55 applies a cardiac therapy while the other IPG 55 applies anobstructive sleep apnea therapy.

FIG. 2A is a block diagram schematically illustrating an implantablestimulation system 100, according to one embodiment of the presentdisclosure. In one embodiment, system 100 comprises at leastsubstantially the same features and attributes as system 10 of FIG. 1.As illustrated in FIG. 2A, system 100 includes a sensing module 102, astimulation module 104, a therapy module 106, and a patient managementmodule 108. In one embodiment, the IPG 109 of therapy module 106comprises at least substantially the same features and attributes as IPG55 of FIG. 1.

Via an array of parameters, the sensing module 102 receives and trackssignals from various physiologic sensors (such as a pressure sensor,blood oxygenation sensor, acoustic sensor, electrocardiogram (ECG)sensor, or impedance sensor) in order to determine a respiratory stateof a patient, whether or not the patient is asleep or awake, and otherrespiratory-associated indicators, etc. Such respiratory detection maybe received from either a single sensor or any multiple of sensors, orcombination of various physiologic sensors which may provide a morereliable and accurate signal.

For example, in one embodiment, the sensing module 102 comprises asensing monitor 120, as illustrated in FIG. 2B. The sensing monitor 120includes a body parameter 130, which includes at least one of aposition-sensing component 132 or a motion-sensing component 134. In oneembodiment, the motion-sensing component 134 tracks sensing of “seismic”activity (via an accelerometer or a piezoelectric transducer) that isindicative of walking, body motion, talking, etc. In another embodiment,the position-sensing component 132 tracks sensing of a body position orposture via an accelerometer or other transducer. In some embodiments,body parameter 130 utilizes signals from both the position-sensingcomponent 132 and the motion-sensing component 134.

In some embodiments, sensing monitor 120 additionally comprises one ormore of the following parameters: an ECG parameter 136; a time parameter138; a bio-impedance parameter 140; a pressure parameter 142; and ablood oxygen parameter 144. In one aspect, the pressure parameter 142includes a respiratory pressure component 143. In one aspect, the timeparameter 142 tracks time generally (e.g. time intervals, elapsed time,etc.) while in other aspects, the time parameter 142 tracks the time ofday in addition to or instead of the general time parameters. In anotheraspect, the time parameter 142 can be used to activate or deactivate atherapy regimen according to a time of day.

It is also understood that system 100 (FIG. 2A) would include, or beconnected to, the analogous physiologic sensor (e.g., LED-type tissueperfusion oxygen saturation) implanted within or attached to the body ofthe patient to provide data to each one of their respective parameters(e.g., blood oxygenation parameter 144) of the sensing monitor 120. Insome embodiments, sensing monitor 120 also includes a target nerveparameter 146 which represents physiologic data regarding the activityof a nerve to be stimulated, such as the hypoglossal nerve, includingspecification of the trunk and/or one or more branches of thehypoglossal nerve.

In other embodiments, the target nerve comprises another nerve (otherthan the hypoglossal nerve) that facilitates a therapy regimen to treatobstructive sleep apnea. In yet other embodiments, sensing monitor 120also includes an acoustic sensing parameter 147 which representsphysiologic data from respiratory airflow or cardiac activity that issensed acoustically and that is indicative of respiratory effort.

In further reference to FIG. 2A, therapy manager 106 of system 100 isconfigured to automatically control initiation, termination, and/oradjustment of a sleep apnea therapy, in accordance with the principlesof the present disclosure. Therapy manager 106 also tracks and appliesvarious treatment parameters, such as an amplitude, pulse width,electrode polarity, duration, and/or frequency of a neuro-stimulationsignal, in accordance with a treatment protocol programmed into thetherapy manager 106.

In one embodiment, therapy manager 106 comprises one or more processingunits and associated memories configured to generate control signalsdirecting the operation of system 100, including at least sensing module102, therapy manager 106, stimulation module 104, and patient managementmodule 108. In particular, in response to or based upon commandsreceived via an input and/or instructions contained in the memoryassociated with the controller in response to physiologic data gatheredvia the sensing module 102, therapy manager 106 generates controlsignals directing operation of stimulation module 104 to selectivelycontrol stimulation of a target nerve, such as the hypoglossal nerve, torestore airway patency and thereby reduce or eliminate apneic events.

With this in mind, therapy manager 106 acts to synthesize respiratoryinformation, to determine suitable stimulation parameters based on thatrespiratory information, and to direct electrical stimulation to thetarget nerve. While any number of physiologic parameters can be usedwith varying success to detect an apnea, in one embodiment of thepresent disclosure, the sensing module 102 detects apneas via a thoracicbio-impedance parameter. In particular, a measurement of thoracicimpedance is used to track the relative amplitude of the respiratorywaveform. Physiologically speaking, the bio-impedance of the lungsvaries as the lungs fill and empty with air. Accordingly, thoracicimpedance increases during inspiration and decreases during expiration.In another aspect, a varying respiratory drive will also cause theamplitude of the bio-impedance to vary, with a larger respiratory driveincreasing the signal amplitude of the bio-impedance. In one embodiment,the vector providing the bio-impedance measurement is predominantlylung-volume related, and not due to diaphragm displacement or cardiacdisplacement during respiration.

Upon obtaining the bio-impedance signal, the bio-impedance signal isfurther processed to identify an average peak amplitude over time. Anapnea is detected by further identifying cyclic amplitude variationsthat occur for a duration substantially similar to the already knownduration of a typical apneic event.

For purposes of this application, the term “processing unit” shall meana presently developed or future developed processing unit that executessequences of instructions contained in a memory. Execution of thesequences of instructions causes the processing unit to perform stepssuch as generating control signals. The instructions may be loaded in arandom access memory (RAM) for execution by the processing unit from aread only memory (ROM), a mass storage device, or some other persistentstorage, as represented by a memory associated with the controller. Inother embodiments, hard wired circuitry may be used in place of or incombination with software instructions to implement the functionsdescribed. For example, the controller may be embodied as part of one ormore application-specific integrated circuits (ASICs). Unless otherwisespecifically noted, the controller is not limited to any specificcombination of hardware circuitry and software, nor limited to anyparticular source for the instructions executed by the processing unit.

In general terms, the stimulation module 104 of system 100 is configuredto generate and apply a neuro-stimulation signal via electrode(s) (suchas stimulation electrode(s) 65) according to a treatment regimenprogrammed by a physician and/or in cooperation with therapy manager106.

In general terms, the patient management module 108 is configured tofacilitate communication to and from the IPG 109 in a manner familiar tothose skilled in the art. Accordingly, the patient management module 108is configured to report activities of the IPG 109 (including sensedphysiologic data, stimulation history, number of apneas detected, etc.)and is configured to receive initial or further programming of the IPG109 from an external source, such as a patient programmer, clinicianprogrammer, etc.

FIG. 3A schematically illustrates a lead 150 in one exemplary embodimentof the implantable stimulation system 10 of FIG. 1. As shown in FIG. 3A,lead 150 is configured to be delivered transvenously and to bepositioned within the vasculature. Lead 150 is configured to place astimulation electrode portion 156 within the ranine vein 188 adjacentthe hypoglossal nerve 190 (or another vein adjacent the hypoglossalnerve or another target nerve). In one aspect, the ranine vein is thevena comitans of the hypoglossal nerve, which begins at its distal endat a point below the front of the tongue, travels along the distalportion of the hypoglossal nerve, and then may join the lingual vein,and eventually opens into the internal jugular vein. In another aspect,other veins, such as another branch of the lingual vein may also be acandidate for the simulation electrode placement instead of the raninevein or in addition to the ranine vein.

Accordingly, lead 150 is employable in a method of transvenouslydelivering a stimulation electrode to stimulate a target nerve. In thismethod, as illustrated in FIG. 3A, lead 150 is introduced into andthrough the subclavian vein 182 and then is advanced through the jugularvein 184, through vein trunk 186, and into the ranine vein 190(otherwise known as the vein comitans of the hypoglossal nerve) untilstimulation electrode portion 156 is within a desired position of theranine vein 180 (or another vein adjacent a target nerve).

In some embodiments, the neuro-stimulation signal is applied at a singlestimulation site along the hypoglossal nerve or another target nerve, asillustrated in FIG. 3A. However, in other embodiments, theneuro-stimulation signal of a sleep apnea therapy is applied from one ormore of multiple locations 230, 232, 234, 240, 242, 244 (represented bythe symbol x) within one or more veins to target multiple stimulationsites 190P, 190M, 190D along a target nerve 190, as schematicallyillustrated in FIG. 4A. The electric field applied at each site isrepresented schematically by the directional arrow extending from thesymbol x toward the stimulation site 190M, 190P, 190D on nerve 190. Inone aspect, these multiple sites include multiple stimulation locationsarranged proximally (e.g., location 230), midway (e.g. location 232),and distally (e.g., location 234) within vein 231 along the hypoglossalnerve 190, one or more stimulation locations on both the right and lefthypoglossal nerves, and/or multiple stimulation locations (proximal 240,midportion 242, and distal 244) along another vein 235 adjacent to thehypoglossal nerve 190. While FIG. 4A depicts three stimulation sites orregions 190P, 190M, 190P on the target nerve, it is understood thatembodiments of the present disclosure are employable to stimulate nerve190 at any point (or multiple points) between (or distally beyond orproximally beyond) the identified regions 190P, 190M, 190P along nerve190.

It is understood, as illustrated in FIG. 4B, that in some embodiments, astimulation lead system 275 includes two or more stimulation leads276,277 that extend from an IPG 55 (FIGS. 1-2) to enable the separateleads 276,277 to extend down each of the respective differenttransvenous pathways to enable two or more independent stimulationlocations on a single target nerve from different veins, such as veins231 and 235 (FIG. 2). In one aspect, each separate lead includes one,two, or more different electrode portions 280, 282, 284 spaced apartfrom each other along a length of the distal portion 279 of each lead276, 277, as further illustrated in FIG. 4B. In some embodiments, theelectrode portions 280, 282, 284 of each lead 276, 277 are arranged witha minimum distance (D1 or D2) therebetween such that the stimulationsignal applied at one electrode portion is separate and independent fromthe stimulation signal applied at the other electrode portions toachieve independent stimulation sites along the same target nerve.Accordingly, the electrode portions of a distal portion of one lead arespaced apart such that when a stimulation signal from a first electrodeportion (e.g., electrode portion 280) is applied at one site, the otherrespective sites are not stimulated by the first electrode portion. Ofcourse, it is also understood that each of the electrode portions 280,282, 284 can be activated simultaneously to simultaneously apply asignal to each of the spaced apart, independent stimulation sites.

In some embodiments, the spacing D1 and D2 between the electrodes on thefirst lead 276 is equal to each other and the spacing D3 and D4 betweenthe electrodes on the second lead 277 is equal to each other. In someother embodiments, the spacing D1 and D2 between the electrodes on thefirst lead 276 (or the spacing D3 and D4 between the electrodes on thesecond lead 277) is substantially different from each other. In someembodiments, the spacing (D1, D2) between the electrodes on the firstlead 276 is the same as the spacing (D3, D4) between the respectiveelectrode portions on the second lead 277. However, in otherembodiments, the spacing (D1, D2) between the electrodes on the firstlead 276 are the different than the spacing (D3, D4) between theelectrode portions on the second lead 277 to account for the differentdistances traveled transvenously by the respective leads 276, 277 tolocate the different respective electrode portions at desiredstimulation sites.

It is understood that in other embodiments, the transvenously accessiblestimulation sites along one or more nerves are spaced apart from eachother by a distance that requires the application of stimulation signalsto enable capturing the corresponding portion of the target nerve butwherein the spacing between adjacent stimulation sites along the nerveis close enough to allow some overlap between the adjacent stimulationsignals.

In some embodiments, the separate stimulation leads 276, 277 oftransvenous lead system 275 are positioned transvenously withindifferent veins (e.g., 231 and 235 or a different set of veins) tostimulation different nerves. In this arrangement, one transvenous lead276 stimulates a first nerve (such as nerve 190) and the othertransvenous lead 277 stimulates a second nerve (not shown). In oneaspect, each of the first and second nerves are associated with controlof the respiratory system such that their selective stimulation relativeto a respiratory pattern restores and maintains airway patency toalleviate obstructive sleep apnea.

Referring again to FIG. 3A, in some embodiments a nerve integritymonitor (stand alone monitor 190 or integrated into a sleep apneaphysician programmer 108, such as programmer 108 in FIG. 2) is used toaide the physician in placing the electrode portion 156 of lead 150 inthe proper location. In this regard, in one embodiment, the nerveintegrity monitor comprises at least substantially the same features andattributes as the nerve integrity monitor described in U.S. Pat. No.6,334,068, entitled INTRAOPERATIVE NEUROELECTROPHYSIOLOGICAL MONITOR,issued on Dec. 25, 2001, and which is hereby incorporated by referencein its entirety. In other embodiments, other nerve integrity monitors oran equivalent array of instruments (e.g., a stimulation probe andelectromyography system) are used to apply the stimulation signal andevaluate the response of the muscle innervated by the target nerve.

In one embodiment, nerve integrity monitor 190 is further illustrated inFIG. 3B and comprises stimulation module 192 and a response module 194that includes electromyography monitoring electronics (EMG) 196.

With this in mind, FIG. 3B further illustrates a response evaluationarray 300, according to one embodiment of the present disclosure. Asshown in FIG. 3B, response evaluation array 300 provides one or moremechanisms to evaluate the effectiveness of a target site forstimulating a target nerve. In one embodiment, the array 300 includes:(1) observing or measuring the extent and location (an extension of thebase of the tongue is preferred over extension of the tip) of tonguemotor response 304, such as but not limited to tongue protrusion(indicated by arrow P); (2) observing or measuring the extent ofincreased cross-sectional area (indicated by arrow W) of an upperrespiratory airway 302; (3) measuring the extent of an EMG response 306(measured via EMG electronics 196 of monitor 190) of one or more musclesupon stimulation applied at a potential target site within a vein; (4)observing or detecting a twitch of the tongue or laryngeal muscle;and/or (5) a substantial reduction in apnea events.

Accordingly, with this in mind, monitor 190 and one or more aspects ofthe response array 200 is used to evaluate the positioning of a leadwithin a vein relative to a potential stimulation site on a targetnerve. In one aspect, a repetitive stimulation pattern is applied fromthe stimulation module 192 of nerve integrity monitor 190 to theelectrode portion 156 of lead 150 as the lead 150 is advanced distallyduring navigation of the ranine vein (or other vein). In someembodiments, the applied stimulation pattern is a 1 second burst ofstimulation every 3 seconds, a ramping stimulation pattern, and/or aphysician controlled burst. In another aspect, electromyography (EMG)monitoring electronics 196 of the nerve integrity monitor 190 enablesmeasuring a muscle response to the nerve stimulation applied duringnavigation of the target veins. Accordingly, fine wire electrodes 308(or similar) are connected in electrical communication with the nerveintegrity monitor 190 and are used to continuously monitor the muscleactivity in response to the stimulation patterns applied via electrodeportion 156 during navigation of the lead 150. Using this arrangement,this closed loop feedback will allow the physician to obtain real-timefeedback of a position (along the transvenous pathway) of the electrodeleads 156 and feedback regarding the ability of the electrode leads 156to capture the target nerve at a particular position of the electrodeleads 156 along the transvenous pathway adjacent the target nerve. It isalso understood that the methods described in association with FIGS.1-3B for placement of lead 150 are applicable to placement of otherleads described in association with FIGS. 4A-14.

In order to advance and deliver the electrode portion 156 of lead 150 tothe target location, one embodiment of the present disclosure employs adelivery mechanism, such as one of the delivery mechanisms illustratedin FIGS. 5A-5B. In most instances, it is expected that the stimulationlead is introduced into a subclavian vein, however, other entry sitesare not strictly excluded.

As illustrated in FIG. 5A, an over-the-wire lead system 200 includes animplantable lead 202 including at least one lumen (not shown) slidablyadvancable over a guide wire 204. In use, distal end 206 of steerableguide wire 204 is advanced through the vasculature 180 (FIG. 3A) to thetarget location and then lead 202 is advanced over the proximal portion205 of guide wire 204 (and along the length of guide wire 204) untilelectrode portion 208 of lead 202 is located at the target stimulationsite. In one aspect, lead 202 is in electrical communication with IPG 55(FIG. 1) to enable IPG 55 to control operation of electrode portion 208of lead 202. It is also understood that once electrode portion 208 islocated optimally along a length of the vein (through which it extends),the lead 202 can be rotated to thereby rotate the electrode portion 208to apply different stimulation effects to the various fascicles of thetarget nerve.

In another embodiment, a stylet-driven mechanism is employed to deliverelectrode portion 156 of lead 150 to the target location to stimulatethe hypoglossal nerve (or another target nerve). With this in mind, FIG.5B illustrates a stylet lead system 220 that includes a lead 222 securedto a guide wire 224. In use, distal end 226 of steerable lead 222 isadvanced through the vasculature 180 via advancing and steering guidewire 224 until electrode portion 228 of lead 222 is located at thetarget stimulation site. In one aspect, lead 202 is in electricalcommunication with IPG 55 (FIG. 1) to enable IPG 55 to control operationof electrode portion 228 of lead 220.

Referring again to FIG. 3A, in the one embodiment, lead 150 includes alead body 152 that supports a respiratory sensor 154 (including firstportion 155A and second portion 155B) at a proximal portion of lead body152. In other words, the respiratory sensor 154 is provided on the samelead body 152 as the electrode portion 156 so that both the respiratorysensor 154 and the electrode portion 156 are placed in the vasculature180 in a single pass. With this arrangement, as the electrode portion156 is advanced distally for placement adjacent a target nerve, therespiratory sensor 154 becomes automatically placed within a pectoralregion of the patient 20 to enable sensing the respiration pattern ofthe thorax of the patient. With this placement, the sensor 154 detectsrespiratory features and/or patterns (e.g., inspiration, expiration,respiratory pause, etc.) in order to trigger activation of electrodeportion 156 to stimulate a target nerve. Accordingly, with thisarrangement, the IPG 55 (FIG. 1) receives sensor waveforms from therespiratory sensor 154, thereby enabling the IPG 55 to deliverelectrical stimulation synchronously with inspiration, such as with eachrespiratory breath (or another aspect of the respiratory pattern relatedto inspiration) according to a therapeutic treatment regimen inaccordance with embodiments of the present disclosure. It is alsounderstood that the respiratory sensor 154 is powered by the IPG 55 andthe IPG 55 also contains internal circuitry to accept and process theimpedance signal from the lead 150.

In some embodiments, a respiratory waveform is monitored and stimulation(generally synchronous with respiration) is not applied until arespiratory feature and/or pattern indicative of an apnea is identified.Stimulation is terminated upon detection that the apneic-indicativefeature or pattern is no longer present within the monitored respiratorywaveform.

In one embodiment, the respiratory sensor 154 is an impedance sensor. Inone aspect, the impedance sensor is configured to sense a bio-impedancesignal or pattern whereby the control unit evaluates respiratorypatterns within the bio-impedance signal. For bio-impedance sensing, inone embodiment, electric current will be injected through electrode 155Band an electrically conductive portion of case 56 of the IPG 55 (FIG.3A) and voltage will be sensed between electrode 155A and 155B (or alsobetween 155A and the electrically conductive portion of case 56 of IPG55) to compute the impedance.

In another embodiment of bio-impedance sensing, during the placement ofthe impedance sensing lead, the impedance waveform can be displayed onthe programmer (108) in real time. The location of electrodes 155A and155B can be interactively (an array of electrodes would be available toselect from via a multiplexer switch within the IPG) adjusted to yieldthe optimal signal to noise ratio in represent the respiratory phaseinformation.

In another embodiment, the sensor 154 is a pressure sensor. In oneaspect, the pressure sensor in this embodiment detects pressure in thethorax of the patient. In another aspect, this pressure could be acombination of thoracic pressure and cardiac pressure (e.g., bloodflow). With this configuration, the controller is configured to analyzethis pressure sensing information to detect the respiratory patterns ofthe patient.

In some embodiments, lead 150 includes an anchor 158 that is locatableat a proximal portion of lead body 152. The anchor 158 is configured toensure that sensor 154 and electrode portion 156 remain in the properposition within the vasculature 180.

The previously introduced FIGS. 1 and 3A generally depict a stimulationelectrode portion 65,156 transvenously delivered into the ranine vein(i.e., the vena comitans of the hypoglossal nerve) to enable stimulatingthe hypoglossal nerve to treat sleep apnea. In one embodiment of thepresent disclosure, as illustrated in FIG. 6, a method 250 of treatingapnea includes identifying an optimal site to locate stimulationelectrode portion 156 (FIG. 3A) along a length of the ranine vein (oranother vein suitable to apply stimulation to the hypoglossal nerve oranother target nerve) that will result in a desired stimulation of thehypoglossal nerve. In particular, as illustrated in FIG. 6, in a firststep 252 the lead 150 is advanced through the vasculature 180 (FIG. 3A)to a range of target sites within the ranine vein (or other nearby vein)and a pre-determined electrical stimulus is applied at each potentialtarget site along the ranine vein (at 254). As illustrated at 256, uponthe application of the electrical stimulus at each potential targetsite, the response to the stimulation is identified by: (1) a degree oftongue protrusion; (2) the size of cross-sectional area of the upperairway; (3) a best EMG response indicative of maintaining airwaypatency; and/or 4) a twitch from either the tongue or laryngeal muscle.As illustrated at 258, using the response data for each potential targetsite, the method 250 identifies one or more treatment sites (from amongthe potential target sites along the ranine vein) correlated with thegreatest impact on maintaining airway patency during inspiration.

It is also understood that these steps 252-258 can be repeatediteratively, as necessary, until the optimal vein and the optimalstimulation location along that vein are identified. With this in mind,in employing method 250, one or more venous pathways might be exploredbefore one or more veins (and a location along that vein(s)) areidentified as being an optimal site(s) from which to apply an electricalstimulus. In other words, method 250 is not limited to evaluating targetsites within a single vein adjacent a target nerve, but extends toevaluating several different veins adjacent to one or more targetnerves. In this regard, method 250 is employed to identify the vein fromamong a group of veins that enables providing the most efficaciousstimulus to a target nerve (e.g., nerves innervating the muscles of theupper airway including the genioglossal, hypoglossus, palatoglossus,etc.), and to identify the best location along one of the those sites toprovide the most efficacious stimulus. As previously mentioned, in someembodiments, more than one vein is identified and used so that astimulation signal is applied from two different veins toward the targetnerve.

In one aspect, in evaluating multiple potential stimulation sites alonga vein or along multiple veins, at each site the method 250 iterativelyapplies a stimulation signal with differing values for each signalparameter (e.g., polarity, pulse width, frequency, and amplitude) todetermine which combination of values yields the best impact of thestimulation signal upon the target nerve at a potential site. In thisway, each potential site is evaluated under conditions in which thestimulation signal would actually be applied were that potential sitechosen as an optimal site for stimulation. In one embodiment, thisdetermination of an optimal stimulation site via evaluating each of thestimulation parameters employs therapy module 106 in cooperation withstimulation module 104, a stimulation lead 150, and patient programmingmodule 108, as previously described in association with FIGS. 1-3A.

FIG. 7 illustrates a stimulation lead system 350 to be deployed insteadof lead 150, according to one embodiment of the present disclosure. Leadsystem 350 comprises substantially the same features and attributes aslead 150 (FIG. 3) except for providing the sensing portion along aseparate lead body 382 from the lead body 352 that supports astimulation electrode portion (not shown, but similar to electrodeportion 156 in FIG. 3A). Accordingly, as illustrated in FIG. 7, leadsystem 350 includes a pair of lead bodies 352 and 382 with lead body 352dedicated to supporting the stimulation electrodes and with lead body382 dedicated to support the sensor 354. The lead body 382 supportssensor 354, including first portion 355A and second portion 355B spacedapart from each other along a length of lead body 382. In oneembodiment, the lead body 382 has a length configured to orient both thefirst portion 355A and the second portion 355B within the subclavianvein 182. However, in other embodiments, the lead body has a lengthconfigured to orient one or both of the first portion 355A and thesecond portion 355B within one or more portions 189 of the vasculature180 beyond the subclavian vein 182. In any case, sensor 354 isconfigured to monitor respiratory effort to detect patterns indicativeof apneas/hypopneas, and to detect the patterns of inspiration,expiration, and/or respiratory pause, which may be used to trigger atherapeutic stimulation.

In some embodiments, sensor lead 382 of lead system 350 is not placedtransvenously but is implanted subcutaneously, either adjacent to thepocket housing the IPG 55 or tunneled within tissue in the pectoralregion surrounding the IPG 55. In other embodiments, sensor lead 382additionally comprises a cardiac lead (epicardial or intra-cardiac) thatis also used for a cardiac therapy (for example, therapies such asbradycardia, tachycardia, or heart failure).

While various different shapes and forms of leads can be used in themethods and systems of the present disclosure, FIGS. 8-14 illustrateseveral different exemplary embodiments of leads. In at least some ofthese embodiments, a fixation mechanism provides releasable fixation fora stimulation lead so that transvenous placement of a stimulation leadcan be maintained for semi-permanent time period or can be reversed(i.e., removed) if necessary.

FIG. 8 is a side plan view schematically illustrating a lead 400including a lead body 402 having a proximal portion 404 and a distalportion 406, which supports a stimulation electrode array 409. Theelectrode array 409 includes one or more surface electrodes 410 spacedapart along a length of the distal portion 406 of the lead body 402. Insome embodiments, lead 400 includes an anchor 408 at the proximalportion 404 of lead body 402, which is configured to maintain theposition of the lead body 402 relative to a length of the vein(s)through which the lead body 402 extends. In one aspect, this anchor 408facilitates maintaining the position of the stimulation electrode array409 at a desired site within the vein adjacent a desired stimulationsite of the target nerve.

Once implanted, a transvenous stimulation system for automaticallytreating obstructive sleep apnea must remain stable and endure thenormal activities of the patient. For example, the neck of a patientmoves through a wide range of motion through many different positions.To counteract the potential for a stimulation lead to move back andforth within a vein (relative to a desired stimulation site),embodiments of the present disclosure provide an anchoring mechanism toanchor a distal portion of a stimulation lead within a vein at thedesired stimulation site relative to a target nerve. These anchoringmechanisms insure that proper placement of the stimulation lead ismaintained despite the dynamic motion and varying positions of the neck,which could otherwise cause inadvertent repositioning of the stimulationlead (relative to the target nerve) if the distal anchoring mechanismswere not present. Several embodiments of a distal anchoring mechanismare described and illustrated in association with FIGS. 9 and 11-14.

FIG. 9 is a side plan view schematically illustrating a lead 430including a distal anchoring mechanism, in accordance with oneembodiment of the present disclosure. In this embodiment, a lead 430includes a lead body 432 having a proximal portion 434 and a distalportion 436, which supports a stimulation electrode array 439, asillustrated in FIG. 9. The electrode array 439 includes one or moresurface electrodes 440 spaced apart along a length of the distal portion436 of the lead body 432. In another aspect, distal portion 436 of leadbody 432 comprises a distal anchoring mechanism arranged as a coiledconfiguration 450 and which is configured to maintain the position ofthe lead body 402 relative to a length of the vein(s) through which thelead body 402 extends. This coiled configuration acts to fix the distalportion 436 of the lead body 432 within the vein at the location atwhich the electrodes 440 will apply an electrical stimulus. In oneaspect, prior to insertion of the lead 430 into the venous system, thedistal portion 436 is in the coiled configuration 450. However, in orderto install the lead 432 into the venous system, the distal portion 436is converted from the coiled configuration 450 into a generally straightconfiguration (i.e., lacking coils) by advancing the guide wire throughat least the distal portion 436 of the lead body 432. After maneuveringthe guide wire and the lead 430 to the desired location within thevenous system, the guide wire is removed proximally from the lead body432, which allows the distal portion 436 to return to the coiledconfiguration 450. In one embodiment, this “memory effect” of the coiledconfiguration is achieved via incorporating materials such as Nitonal orthermo-formed polyurethane into the distal portion 436. In otherembodiments, other materials having memory behavior, as known by thoseskilled in the art, are employed to form distal portion 436, therebyenabling the operation of coiled configuration 450.

In another aspect, as previously described in connection with method250, each of the various stimulation parameters (for example, electrodepolarity, amplitude, frequency, pulse width, and duration) are tested ateach potential stimulation site as the stimulation lead 430 ismaneuvered (through the venous system) adjacent to the target nerve. Byevaluating the response at each location along the venous system (in thetarget nerve region) and noting the particular value or combination ofstimulation parameters that yields the best response at that potentiallocation, one can determine the optimal stimulation site for stimulationelectrode array 439. As previously described herein, this method ofdetermining a stimulation site (according to an effective group ofcorresponding values for the stimulation parameters) can be applied toanyone of the different stimulation electrode configurations within thispresent disclosure.

In another embodiment of the stimulation leads and as previouslydescribed in association with FIGS. 1-4B, two individual branches of thestimulation lead or two independent stimulation leads can be placedtransvenously near both left and right side of the hypoglossal nerve.The IPG and programmer can control stimulation delivery to each branchesof the stimulation lead either independently or dependently.

FIG. 10 is a perspective view illustrating another embodiment of thepresent disclosure. In this embodiment, a lead 500 includes an array ofring electrodes 502, 504, 506 at a distal portion of the lead 500 andwhich is configured to apply an electrical stimulus to a target nerve.In one aspect, this array of ring electrodes 502-506 is configured todirect an electrical field to a target nerve (e.g., hypoglossal nerve)spaced apart from the lead 500 within the vein (e.g., ranine vein). Itis also understood that the ring electrodes 502-506 can be optionallyemployed in one or more of the other embodiments described inassociation with FIGS. 8-9 and 11-14.

FIG. 11 is a perspective view schematically illustrating a lead 520including a distal anchoring mechanism, in accordance with oneembodiment of the present disclosure. In this embodiment, the lead 520includes a stent portion 522 at a distal portion of the lead 520, and inwhich the stent portion 522 includes one or more stimulation electrodes524, 526, 528 incorporated into (or added onto) the structure (e.g.,struts) of the stent. In one aspect, this array of electrodes 524-528supported by the stent structure 522 is configured to direct anelectrical field to a target nerve (e.g., hypoglossal nerve) spacedapart from the lead 500 within the vein (e.g., ranine vein). Moreover,the stent structure 522 provides a mechanism to secure the location ofthe electrodes 524-528 at a desired placement along a length of the vein(through which the lead 520 extends) corresponding to a desiredstimulation site of a target nerve.

In one embodiment, the stent structure 522 is arranged in a collapsedstate (having a diameter generally represented by A in FIG. 11) duringinsertion into the venous system and the vein adjacent the target nerve.Once the stent structure 522 and associated stimulation electrodes arelocated a potential stimulation site, the physician initiates conversionof the stent structure 522 from its collapsed state to an expanded state(having a diameter generally represented by B in FIG. 11) to contact thewalls of the vein, which in turn, anchors the electrodes in place. Inother words, the stent structure 522 acts as a distal fixation mechanismthat fixates the distal portion of the lead within the vein at thedesired stimulation site. In one aspect, during the process ofevaluating different potential stimulation sites, the stent structure istemporarily expanded to test the effectiveness of a stimulation signalat a potential stimulation site and then re-collapsed to enablerepositioning the lead 520 along the vein to place the electrodes andstent structure at a different potential stimulation site. This processis repeated as many times as necessary until the optimal stimulationsite is determined, where the stent structure 522 is then re-expanded tosecure and maintain the distal portion of the lead 520 at the optimalstimulation site. It is understood that the selective expansion,collapse, and final fixation of the stent structure in an expanded stateis performed according to techniques known in the art, such asmanipulating the stent structure 522 via rotation, pushing, and/orpulling of a guide wire.

In other embodiments, instead of using the coiled configuration 350 ofFIG. 9 or the stent structure of FIG. 11, fixation of a distal portionof a stimulation lead within a vein is achieved via other mechanisms.

FIGS. 12A-12B schematically illustrate a transvenous stimulation lead530 including a distal fixation mechanism, according to one embodimentof the present disclosure. As illustrated in FIG. 12A, a distal portion531 of the stimulation lead 530 includes a distal fixation mechanismprovided via an array 532 of deployable tines 534. In FIG. 12A, tines534 are shown in a deployed configuration in which tines 534 extendradially from the body of distal portion 531 of lead 530. In thisposition, the tines 534 are configured to releasably engage the walls ofa vein to thereby anchor the distal portion 531 within the vein. It isunderstood that the tines are configured in a manner as to notnegatively impact the integrity of the walls of the vein.

In one aspect, as the distal portion of the lead is advanced through thevenous system, a guidewire is used to position these tines 534 into astorage position generally against an outer wall of the lead, asschematically illustrated in FIG. 12B. After a suitable stimulation sitehas been determined, the tines 534 are deployed (i.e., selectivelyexpanded radially outward away from the outer wall of the lead as shownin FIG. 12A) to engage the walls of the vein to thereby anchor thedistal portion 531 of the lead at the desired stimulation site alongthat vein (and adjacent to the desired location along the target nerve).In some embodiments, the deployable tines 534 are made of a polyurethanematerial and/or a Nitonal spring.

It is understood that the array 532 of tines 534 is located on distalportion 531 of lead 530 at a position sufficiently close to an electrodestimulation portion of lead 530 (such as one of the electrodeconfigurations illustrated throughout this application) to insure thatthe electrode stimulation portion is generally fixed within a vein at alocation corresponding to a desired stimulation site of a target nerve.

FIG. 13 is a perspective view illustrating a transvenous stimulationlead 540 configured to apply an electrical stimulus to a target nerve,according to another embodiment of the present disclosure. In thisembodiment, the lead 540 includes a series 541 of programmable arrays542, 544, 546 of electrode portions 548 with the respective arrays 542,544, 546 spaced apart from each other along a length of the distalportion of the lead 540. In one aspect, the respective electrodeportions 548 of each array extend circumferentially about an outersurface of lead 540 in a spaced apart relationship to form a generalring-shaped configuration. In one aspect, the programmable arrays542-546 of electrode portions 548 are configured to direct an electricalfield from a location within the vein (e.g., ranine vein) to a targetnerve (e.g., hypoglossal nerve) spaced apart from the lead 540. It isalso understood that the arrays 542-546 of electrodes can be optionallyemployed in one or more of the other embodiments described inassociation with FIGS. 8-9 and 11-12B.

In one embodiment, each array 542, 544, 546 of electrodes comprises two,three, four or more independent electrode portions 548. In one aspect,the electrode portions 548 are independently programmed to stimulationthe target stimulation site. In other words, at any given time, astimulation signal is applied from zero, one, two, or more electrodeportions 548 of each separate array 542-546. In this embodiment, themany varied positions of the electrode portions both along the length ofthe distal portion of the lead 540 and circumferentially or radiallyabout the lead 540 enables precise activation of selective groups ofelectrode portions 548 (at their various spaced apart locations) toproduce a stimulation signal at virtually any point relative to thedistal portion of lead 540. Accordingly, this arrangement enablesstimulation of a target nerve (or select portions/fascicles of a targetnerve) with little or no rotation of the lead 540 to direct thestimulation to the target stimulation site.

FIG. 14 is a perspective view illustrating a transvenous stimulationlead 560 configured to apply an electrical stimulus to a target nerve,according to another embodiment of the present disclosure. In thisembodiment, a lead 560 includes a programmable array of ring electrodes562 mounted at a distal portion 564 of the lead 560. In one aspect, thisprogrammable array of ring electrodes 562 is configured to direct anelectrical field from the location of the respective ring electrodes 562within the vein (e.g., ranine vein) to a target nerve (e.g., hypoglossalnerve) spaced apart from the lead 560. It is also understood that thering electrodes 562 can be optionally employed in one or more of theother embodiments described in association with FIGS. 8-9 and 11-12B. Inone embodiment, each ring 562 may be independently programmed tostimulate the target stimulation site. In this embodiment, the manyvaried positions of the ring electrodes 562 along the length of thedistal portion of the lead 560 enables precise activation one, two, ormore ring electrodes 562 (at their various spaced apart locations) toproduce a stimulation signal at virtually any point along a length ofthe distal portion of lead 560. Accordingly, this arrangement enablesstimulation of a target nerve with little or no rotation of the lead 560to direct the stimulation to the target stimulation site. Moreover, oncelead 560 is located generally in the region of interest, the lead 560need not be maneuvered extensively distally or proximally within thevein in order to position an electrode adjacent to a desired stimulationsite of a nerve because any one or combination of the ring electrodes562 along the length of the distal portion of the lead are available foractivation to apply a stimulation signal to the target nerve. In oneembodiment, the array of electrodes 562 has a length that substantiallymatches a majority of a length of the hypoglossal nerve, as it extendsfrom a position near the jugular vein toward the genioglossus muscle. Inone aspect, this length of the array enables determining whichelectrodes 562 of the array produce the most efficacious respiratoryairway patency without having to reposition the array within thevasculature. In another aspect, an efficacious respiratory airwaypatency is determined upon identifying which ring electrode 562 orcombination of ring electrodes 562 produces a longest duration ofincreased airway patency, a largest size of increased airway patency,and/or a substantial reduction in apneas.

In this embodiment, the lead does not require rotation of the lead todirect the stimulation to the target stimulation site. Further withmultiple rings attached the control unit, minimal positioning of thelead within the vein is required as optimal stimulation settings may beevaluated using multiple combinations of active or inactive electroderings.

Several different embodiments have been described in association withFIGS. 1-7, in which an IPG 55 is implanted in a pectoral region and inwhich a sensor electrode(s) and a stimulation electrode(s) (extendingfrom the IPG 55) are delivered transvenously to sense respiratorypatterns and to apply a stimulation signal, respectively. In addition,several embodiments of stimulation electrode arrays (and associateddistal fixation mechanisms) have been described in association withFIGS. 8-14. Moreover, it is understood that in some embodiments, a leadis transvenously placed in each side of the body (left and right) suchthat bilateral (simultaneous or alternating) stimulation takes place onthe left and/or right hypoglossal nerve (or other target nerve). Withthese various embodiments in mind, it is further understood that amongthose embodiments, several configurations are provided in which at leasttwo electrodes are spaced apart in the body in the vicinity of the upperairway such that an impedance is measurable between the two spaced apartelectrodes to provide an indication of airway patency (e.g., openingand/or closing of the upper airway). For example, to measure thisimpedance, one of the stimulations electrodes is placed transvenously ona first side of the body and the other one of the stimulation electrodesis placed transvenously on a second side of the body. In someembodiments, this bio-impedance is measured as a trans-thoracicbio-impedance, a trans-laryngeal bio-impedance, or a trans-pharyngealbio-impedance.

In some configurations, the spaced electrodes are both stimulationelectrodes, while in other configurations, the spaced apart electrodescomprise one stimulation electrode and one respiratory sensor electrode.In yet other configurations, the two spaced apart electrodes (used formeasuring an impedance indicative of airway patency) include one of theelectrodes comprising at least one of a stimulation electrode and arespiratory sensor electrode and the other one of the electrodescomprising an electrode formed by an electrically conductive portion ofa case 56 or housing of the IPG 55.

Moreover, in some embodiments, the respective electrodes portionsprovide a dual function in that each electrode provides a respiratorysensing function or a stimulation function as well as acting as a partof a pair of impedance sensing electrodes. On the other hand, in otherembodiments, at least one electrode of the pair of impedance sensingelectrodes does not also act to sense respiration (e.g. inspiration) orto stimulate but rather is dedicated for use in sensing impedance todetect or indicate a degree of airway patency.

Accordingly, by using a pair of electrodes to sense an impedance that isindicative of airway patency, a system operating according principles ofthe present disclosure enables detection of apnea event by indicatingwhether or not a collapse of the airway has taken place. In oneembodiment, this impedance-based indication of airway patency is usedalong with other physiologic sensing information (such as the sensinginformation described at least in association with FIGS. 2A-2B) todetect an apnea event, and to potentially trigger stimulation of atarget nerve to restore airway patency in accordance with theembodiments of the present disclosure.

FIG. 15A is a side plan view schematically illustrating a nervestimulation system 600 for treating obstructive sleep apnea, accordingto an embodiment of the present disclosure. In this embodiment, asillustrated in FIG. 15A, system 600 provides therapy to a patient 602reclined on a support 604 (e.g. a bed) and a headrest structure 606(e.g., pillow), which houses a power source/controller 622 and one ormore radiofrequency transmission coils 620. However, it is understoodthat this embodiment is not strictly limited to a bed 604 and/or pillow,but extends to other furniture configurations in which the patient 602can remain stationary for an extended period of time. As furtherillustrated in FIG. 15A, system 600 includes a microstimulator 635 whichis delivered transvenously into the ranine vein 188 (or other nearbyvein) for stimulating the hypoglossal nerve 190 (or other target nerve),as illustrated in FIG. 15B. In some embodiments, transvenous delivery ofmicrostimulator 635 is accomplished via techniques substantially similarto those previously described in association with FIGS. 9, 11, 12A-12B,as well as via transvenous delivery methods to be further described inassociation with FIGS. 16-17C.

In one embodiment, microstimulator 635 comprises a generally elongatemember including circuitry for generating a neurostimulation signal andat least one electrode 637 arranged on a surface of the micro stimulator635 for transmitting the signal to nerve 190, as illustrated in FIG.15B. In some embodiments, microstimulator 635 comprises a microminiatureelectronic device such as that described in Richmond et al. U.S. Pat.No. 6,240,316, and which is hereby incorporated by reference in itsentirety. However, it is understood that in the context of the presentdisclosure, such micro stimulators are delivered transvenously insteadof being directly implanted into a target muscle.

In general terms, system 600 applies a treatment regimen for treatingobstructive sleep apnea according to sensing methods and stimulationparameters at least substantially the same as those previously describedin association with FIGS. 1-14, including the potential use of bilateralstimulation (for simultaneous or alternate stimulation from the left andright sides of the body) via the use of two separate microstimulators.

Referring again to FIG. 15A, system 600 includes at least one sensingcomponent configured to provide respiratory sensing suitable fordetection of an apnea and for triggering application of the stimulationsignal synchronous with respiration, such as with inspiration. In someembodiments, respiratory sensing is provided via an externally securablebelt 630 including a respiratory pressure sensor 631. Signals sensed atsensor 631 are transmitted wirelessly to power/controller 622 for use inapnea detection and treatment. In other embodiments, respiratory sensingis provided via an impedance sensor 640 which is secured on an externalsurface of a chest via a patch or even implanted subcutaneously. Sensor640 communicates wirelessly with power/controller 622. In someembodiments, belt 630 or the other sensor 640 includes an accelerometeror piezoelectric transducer for detecting body motion/position, withsuch information also being used by controller 622 and/ormicrostimulator 635 to determine when to monitor for apneas and/or whento treat apneas.

In use, as the patient reclines on the support 604, respiratory sensor631 or 640 provides information about respiratory effort which ismonitored via a power/controller 622. Once a treatment threshold isdetected, power/controller 622 generates power which is communicated tomicro stimulator 635 via radiofrequency/transmission coils 620. It isalso understood that in some embodiments, microstimulator 635 storesprogrammed instructions for applying a stimulation signal according toan obstructive sleep apnea treatment regimen, while in other embodimentsmicro stimulator 635 receives such programmed instructions fromcontroller 622 via coils 620. In either case, the instructions are alsoprogrammable by a clinician or by a patient (within certainphysician-authorized constraints). With this in mind, themicrostimulator 635, in turn, selectively stimulates nerve 190 (FIG.15B) according to a treatment regimen to restore airway patency, therebyalleviating the obstructive sleep apnea.

In some embodiments, as illustrated in FIG. 15C, respiratory sensinginformation is obtained via sensors arranged on a garment 675 configuredto be worn by the patient 602 during a time period when apneas mightpotentially occur (e.g. sleeping, resting). In one embodiment, garment675 provides a respiration sensing belt 682 similar to belt 630, whilein other embodiments garment 675 comprises one or more impedance sensorsor other respiratory effort sensors 684 (and/or body motion/positiondetectors) on a pectoral region 680 of the garment 675.

FIG. 16 is a side plan view schematically illustrating an anchoringsystem of a transvenously delivered microstimulator, according to anembodiment of the present disclosure. Accordingly, in some embodiments,as illustrated in FIG. 16, a transvenous delivery mechanism 700 includesa steerable catheter/stylet 710 including a proximal portion 714 and adistal portion 712. The micro stimulator 635 is releasably secured atdistal portion 712 of steerable catheter/stylet 710 via releasemechanism 730. Using techniques known to those skilled in the art,catheter 710 is used to advance and maneuver the microstimulator 635transvenously until adjacent to a desired stimulation site of a targetnerve. At this location, the release mechanism 730 is activated tosecure micro stimulator 635 within the vein adjacent the target nerveand the remainder the catheter 710 is then withdrawn from the veinleaving the microstimulator 635 within the vein. While variousmechanisms can be used to secure the microstimulator 635 within thevein, in this embodiment, an array of selectively deployable tines 720(or other selectively deployable anchors) extends radially outward frommicro stimulator 635 to secure the microstimulator 635 relative to thevein and, thereby relative to the target nerve.

FIG. 17A is a side plan view schematically illustrating a stent-basedanchoring system of a transvenously delivered microstimulator configuredto treat obstructive sleep apnea, according to an embodiment of thepresent disclosure. In this embodiment, a microstimulator 635 is coupledto a stent 770. A steerable catheter/stylet 760 is adapted totransvenously deliver (using techniques known to those skilled in theart) the combination of the stent 770 (in its collapsed state) and themicrostimulator 635 to a location within a vein adjacent a target nerve.Further manipulation of the steerable catheter 760 results in releaseand expansion of the stent 770 to be secured relative to the walls ofthe vein and then withdrawal of the catheter/stylet 760. With thisarrangement, the microstimulator 635 becomes generally fixed relative toa length of the vein and therefore generally fixed relative to a portionof the target nerve.

In some embodiments, micro stimulator 635 is coupled to extend within aninterior 771 of stent 770, as illustrated in FIG. 17B. In oneembodiment, micro stimulator 635 is coupled relative to the stent 770via one or more semi-rigid or resilient tethers 772.

In yet other embodiments, microstimulator 635 is configured to extenddistally forward from (or proximally relative to) an end 773 of stent770 via support 782 (which extends from one or more struts 774), asillustrated in FIG. 17C. accordingly, in this arrangement,microstimulator 635 is not located within the interior 771 (FIG. 17B) ofstent 770, which may lessen any potential interference of the body ofstent 770 relative to the stimulation signal from microstimulator 635.

Embodiments of the transvenously-delivered microstimulator (describedherein) enable precise location of a microstimulator adjacent to anoptimal neurostimulation site because the transvenous approach enablesthe surgeon to vary the position of the microstimulator along the lengthof a vein (using the steerable catheter techniques) and thereby vary theposition of the microstimulator along the length of the target nerve.This method allows the surgeon to identify a precise optimal stimulationsite that causes contraction of one or more specific muscles (suited torestore airway patency) prior to fixing the location of the microstimulator relative to the target nerve. Moreover, steerablecatheter/stylets or other transvenous delivery instruments enablerotation of the microstimulator within the vein to further adjust theeffect of the stimulation on a target nerve or portions of the targetnerve.

Embodiments of the present disclosure provide an implantable system toprovide therapeutic solutions for patients diagnosed with obstructivesleep apnea. The system is designed to stimulate the hypoglossal nerveduring inspiration thereby preventing occlusions in the upper airwayduring sleep.

While at least one exemplary embodiment has been presented in theforegoing detailed description, it should be appreciated that variationsexist. It should also be appreciated that the exemplary embodiment orexemplary embodiments are only examples, and are not intended to limitthe scope, applicability, or configuration of the present disclosure inany way. Rather, the foregoing detailed description will provide thoseskilled in the art with a convenient road map for implementing theexemplary embodiment or exemplary embodiments. It should be understoodthat various changes can be made in the function and arrangement ofelements without departing from the scope of the present disclosure asset forth in the appended claims and the legal equivalents thereof.

The invention claimed is:
 1. A method of treating sleep apnea,comprising: implanting an implantable pulse generator subcutaneously ata pectoral, non-vasculature location within a body of a patient andconnecting a single lead to the pulse generator, wherein the single leadincludes a stimulation electrode portion that is in electricalcommunication with the pulse generator, with the stimulation electrodeportion being separate from, and independent of, stimulation circuitryof the pulse generator; inserting the single lead within a non-cardiacvasculature of the body and advancing the single lead through thenon-cardiac vasculature; and positioning the stimulation electrodeportion of the single lead within the non-cardiac vasculature in closeproximity to the hypoglossal nerve to apply a nerve-stimulation signal,wherein positioning the stimulation electrode portion comprises:arranging the stimulation electrode portion on a distal portion of thesingle lead and arranging a respiratory sensing portion on a proximalportion of the single lead; and distally advancing the single leadwithin the non-cardiac vasculature to simultaneously cause: positioningthe stimulation electrode portion within a first vein of the non-cardiacvasculature in close proximity to the hypoglossal nerve and within aneck region of the patient; and positioning the respiratory sensingportion within a second vein of the non-cardiac vasculature within apectoral region of the patient, the second vein in fluid communicationwith the first vein.
 2. The method of claim 1, wherein applying thenerve-stimulation signal comprises: synchronizing the application of thenerve-stimulation signal with respiration.
 3. The method of claim 2,wherein synchronizing the application comprises: applying thenerve-stimulation signal to occur at each respiratory breath.
 4. Themethod of claim 2, comprising: sensing at least one respiratory featurevia positioning a second respiration sensor on an exterior surface of apatient's body; and wireles sly coupling the second respiration sensorto the implantable pulse generator.
 5. The method of claim 4, whereinsensing the at least one respiratory feature comprises: measuring atrans-thoracic bio-impedance to track the relative amplitude of therespiratory waveform.
 6. The method of claim 4, wherein sensing the atleast one respiratory feature includes additionally measuring at leastone of: a body motion parameter; an electrocardiography parameter; and ablood oxygen parameter.
 7. The method of claim 1, comprising: whereinsensing, via the respiratory sensing portion, the at least onerespiratory feature to track the relative amplitude of the respiratorywaveform, and determining an average peak amplitude based on the trackedrelative amplitudes; and detecting, via the at least one respiratoryfeature, an apneic respiration pattern as cyclic variations of anamplitude of the trans-thoracic bio-impedance relative to the averagepeak amplitude for a duration corresponding to a nominal apneicduration.
 8. The method of claim 1, wherein applying thenerve-stimulation signal comprises: detecting an apneic-indicativerespiratory pattern prior to applying the nerve-stimulation signal;synchronizing the application of the nerve-stimulation signal withrespiration; and discontinuing application of the nerve-stimulationsignal when the apneic-indicative respiratory pattern is no longerdetected.
 9. The method of claim 1, comprising: arranging thestimulation portion to include an array of independently programmableelectrode elements spaced apart from each other along a length of thestimulation portion and spaced apart from each other circumferentiallyon the outer surface of the stimulation portion; and identifying atleast one target site along a length of the hypoglossal nerve viaapplying a stimulation signal to different combinations of the electrodeelements and evaluating which combination of electrode elements achievesan efficacious respiratory airway patency.
 10. The method of claim 1,comprising: arranging the stimulation portion to include an array ofelectrodes spaced apart from each other along a length of thestimulation portion; and identifying at least one target site along alength of the hypoglossal nerve via applying a stimulation signalseparately to each electrode or electrode combination, on aone-at-a-time basis, and evaluating which electrode or electrodecombination achieves an efficacious respiratory airway patency.
 11. Themethod of claim 10, comprising: arranging a length of the array tosubstantially match a majority of a length of the hypoglossal nerveextending from a position near the jugular vein toward the genioglossusmuscle; and determining which electrodes of the array produce theefficacious respiratory airway patency without repositioning thestimulation portion within the non-cardiac vasculature after thestimulation is first positioned in close proximity to the hypoglossalnerve.
 12. The method of claim 10, wherein identifying the at least onetarget portion comprises determining the most efficacious response foreach potential target site via at least one of: determining a degree oftongue motor response; determining an increased cross-sectional area ofan upper respiratory airway; determining a degree of electromyographyresponse of one or more tongue-protrusion related muscles; detecting atwitch from either the tongue or laryngeal muscle; or detecting areduction in apnea events.
 13. The method of claim 10, comprising:determining, at each potential target site of the hypoglossal nerve, atherapeutic neurostimulation signal via applying a test neurostimulationsignal while iteratively varying a value for each signal parameter of aplurality of signal parameters, wherein the signal parameters include atleast one of an amplitude, a pulse width, an electrode polarity, aduration, and/or a frequency.
 14. The method of claim 1, wherein thefirst vein comprises a ranine vein and the second vein comprises asubclavian vein.
 15. The method of claim 1, comprising: arranging therespiratory sensing portion as a first sensing element and a secondsensing element spaced apart from the first sensing element along alength of the single lead.
 16. The method of claim 15, comprising:performing sensing a trans-thoracic bio-impedance relating torespiratory patterns via measuring a voltage across the first sensingelement relative to the second sensing element.
 17. The method of claim1, wherein positioning the stimulation portion comprises: providing thestimulation portion as at least part of an anchoring mechanism;advancing the stimulation portion within the non-cardiac vasculature,with the anchoring mechanism in a generally collapsed state, to a firsttest stimulation site along the hypoglossal nerve; manipulating theanchoring mechanism into an expanded state to engage a side wall of thenon-cardiac vasculature at the first test stimulation site and applyinga first neurostimulation test signal, via the stimulation portion, tothe hypoglossal nerve; manipulating the anchoring mechanism into thegenerally collapsed state to disengage the anchoring mechanism from theside wall of the non-cardiac vasculature and advancing the stimulationportion to a second test stimulation site spaced apart along the lengthof the hypoglossal nerve from the first test stimulation site; andmanipulating the anchoring mechanism into the expanded state tore-engage the side wall of the non-cardiac vasculature and applying asecond neurostimulation test signal, via the stimulation portion, thehypoglossal nerve.
 18. The method of claim 17, comprising providing theanchor mechanism at a distal portion of the single lead as a stentstructure including a generally tubular member, wherein the collapsedstate corresponds to a first diameter of the stent structure and theexpanded state corresponds to a second diameter substantially largerthan the first diameter and sized to engage the side wall of thenon-cardiac vasculature.
 19. The method of claim 1, wherein theimplantable pulse generator includes a power supply and the stimulationelectrode portion is powered via the single lead by the implantablepulse generator.
 20. The method of claim 1, wherein the portion of thesingle lead extending between the implantable pulse generator and thestimulation electrode portion and which provides electricalcommunication between the implantable pulse generator and thestimulation electrode portion is without stimulation circuitry.
 21. Themethod of claim 1, comprising: sensing at least one respiratory featurevia delivering a second respiration sensor subcutaneously within apatient's body external to the non-cardiac vasculature.
 22. The methodof claim 21, wherein sensing the at least one respiratory featureincludes additionally measuring at least one of: a respiratory flowparameter; and a time-of-day parameter.
 23. The method of claim 21,comprising: arranging the second respiration sensor to include at leastan accelerometer; and using measurements from the accelerometer inassociation with application of the nerve-stimulation signal.
 24. Amethod of treating sleep apnea, comprising: implanting an implantablepulse generator subcutaneously at a pectoral, non-vasculature locationwithin a body of a patient and connecting a single lead to the pulsegenerator, wherein a distal portion of the single lead includes astimulation electrode portion that is in electrical communication withthe pulse generator, with the stimulation electrode portion beingseparate from, and independent of, stimulation circuitry of the pulsegenerator; inserting the single lead within a non-cardiac vasculature ofthe body and advancing the single lead through the non-cardiacvasculature; positioning the stimulation electrode portion of the singlelead within a first vein of the non-cardiac vasculature in a neck regionof a patient in close proximity to the hypoglossal nerve to apply anerve-stimulation signal; and arranging at least a first portion of arespiratory sensing portion on a second portion of the single leadproximal to, and spaced apart from, the stimulation electrode portion toposition the first portion of the respiratory sensing portion within asecond vein of the non-cardiac vasculature within the pectoral region ofthe patient, wherein the second vein is in fluid communication with thefirst vein.
 25. The method of claim 24, comprising: arranging at least asecond portion of the respiratory sensing portion to be implanted withinthe body in a location external to the non-cardiac vasculature.
 26. Themethod of claim 24, comprising: arranging at least a second portion ofthe respiratory sensing portion to be worn externally on the patient'sbody.
 27. The method of claim 25, wherein arranging the second portionof the respiratory sensing portion to be at least part of the implantedpulse generator, and comprising: arranging the second portion to includeat least an electrically conductive portion of a case of the implantablepulse generator, and wherein the method further comprises: determiningrespiratory information based on a bio-impedance measurable between therespective first and second portions of the respiratory sensing portion.28. The method of claim 25, comprising: arranging the second portion ofthe respiratory sensing portion to include at least an accelerometer;and using measurements from the accelerometer in association withapplication of the nerve-stimulation signal.
 29. The method of claim 28,wherein the accelerometer is configured to measure a body activityparameter at least partially indicative of sleep apnea behavior.
 30. Themethod of claim 23, wherein the accelerometer is configured to measure abody activity parameter at least partially indicative of sleep apneabehavior.